Multiple Sclerosis is a Spectrum Disorder

Dr. Gayatri Devi is a neurologist at Lenox Hill Hospital in NYC.  She has recently published a book called "The Spectrum of Hope: An Optomistic and New Approach to Alzheimer's Disease and other Dementias."

Dr. Devi is redefining Alzheimer's as a spectrum disorder, meaning that this diagnosis is not the same for every patient, that each patient will have a unique experience, and that there is much which can be done to empower the individual patient to reclaim their health.  A diagnosis of Alzheimer's is not "one size fits all."  And she attacks the biggest myth---that all people with an Alzheimer's diagnosis will end up incompetent in a nursing home.  She says this simply isn't true.

In this new book, Dr. Devi outlines ways to treat and arrest Alzheimer's progression through nutrition, exercise, lifestyle and medication.   She asserts that 60% of all Alzheimer's cases are preventable, and that science has shown that less than 5% of Alzheimer's cases are genetic.   link

I like Dr. Devi.  A lot.  She is positive, informed and uses real data and science to back up her claims. She has worked with Alzheimer's patients for 23 years, and she wants to dispel the myths about the disease.

Dr. Stuart Zola of Emory University has been making the same case.  He has been advocating for a spectrum disorder classification for Alzheimer's Disease and has specific recommendations for treatment.
link

His most important lifestyle interventions are the exact same as Dr. Devi's.
1. Heart Healthy Diet
2. Stress Reduction
3. Exercise
4. Sleep
5. Cognitive training--use it, or lose it.

Does this list look familiar to anyone else?  

I would submit that the exact same case could be made for Multiple Sclerosis.
MS is a neurodegenerative disease which is not genetic.  MS is a vastly different disease in individuals.  MS also occurs more commonly in women.   MS progression can be halted.  MS is a spectrum disorder.

Then why aren't MS neurologists using this same language in discussing treatment and lifestyle intervention with their patients?

The difference is that MS has a $20 billion dollar a year drug industry attached to the diagnosis.  And it is important for MS specialists to maintain the narrative that MS is a destructive, incurable autoimmune disease which must be attacked at the very beginning with immune modulating drugs.  No matter the disease presentation, the age of the patient, the level of neurologic damage---the narrative has been that ONLY drug intervention can arrest the MS disease process.  And this narrative has been pushed and publicized by MS Societies, MS advocacy groups, MS blogs, MS groups (which are sponsored by pharma) and in the press.  There's a lot of money wrapped up in telling this story.

Watch this Canadian news story from 1989, almost 30 years ago.   It will take you 18 minutes, but I believe it is important. The first half is about chemo treatment for MS, the second half is about nutrition.

Link to 5th Estate MS Story

Notice how the neurologists speak to the MS patient about his wheelchair prognosis "in two years" if he does nothing to treat his MS aggressively.   Jeff had a very similar prognosis. He was having trouble walking, was spending the day on the couch, exhausted.  Just like Ron, he was told to "do everything he could" to fight his MS.  But that "everything" only included drug therapy.  Listen to how Ron accepts the risks of cyclophosphamide (Cytoxan), a cancer treatment with very serious side effects,  which would eventually be shown to be ineffective as a monotherapy for MS. link

At 10 minutes in we meet another person with MS.  She has been part of Dr. Roy Swank's 35 year observational study of a low fat diet.  Dr. Swank's patients are still walking, working, living, remaining stable.  Dr. Swank gave his patients hope of disease reversal, of remaining mobile.   His program is simple.  Avoid fats from meat and dairy, eat mostly plants.  What we would call a "heart healthy diet."

The MS neurologist speaks for the medical profession, saying diet has "little to no role" in the care of MS patients.  And this is the position of the MS Society today---even though the science shows that the diet has made a difference.   Again, this was 30 years ago.  And it is still true---as the MS Society threatens to sue Matt Embry for speaking out about true MS Hope, and a program based on the Swank Diet.   link

We need to reframe the dialogue.  MS is a spectrum disorder.  It can be treated with lifestyle, nutrition, and exercise.   A healthy heart and vasculature can protect the brain.   Yes, MS will be different for every individual, medications may help some--and not all will recover.  But that does not negate the very real improvements made for many.

Push back against the pharma narrative.
Write your own story,

Joan

Exciting New MS Treatment!

NEWS RELEASE

A new MS drug appears to alter fluid dynamics and repair the blood brain barrier!
In fact, 63% of the patients treated with Perfuza (toxicmuzab) had no new or enhancing MS lesions at 12 months! In light of recent discoveries of the brain's lymphatic vessels and the connection to venous flow, we are thrilled to be able to offer MS patients a drug treatment which may be addressing CNS fluid dynamics.

Here's more on the impressive results of Perfuza from a recent publication in JAMA---

We found a reduction in the mean number of new brain lesions (corresponding to more lesion- free patients) in the toxicumab group compared with the placebo group at 6 to 12 months. The delayed and positive effect on the magnetic resonance biomarker suggests that toxicumab could affect the dynamic of the blood-brain barrier.

Gadolinium enhancement is a marker of damage to the blood-brain barrier, whose time course depends on lymphatic drainage18 and hence on venous drainage from the skull.19 Previous studies have reported that venous pressure is lowered3 and cerebrospinal fluid dynamics is improved20 after taking toxicmuzab, thereby favoring the drainage of cerebro spinal fluid into the dural veins, which depends on a pressure gradient between the subarachnoid spaces and dural veins.21,22

Another study23 reported that white matter lesion load was inversely correlated with reduced cerebrospinal fluid dynamics, as measured by MRI. In addition, flow improvement through the internal jugular veins owing to toxicmuzab has been reported to improve brain perfusion in patients with RRMS.21 It has also been reported that the development of a new MS plaque was preceded by sustained MRI-detected hypoperfusion before the plaque was identified on MRI.24,25

link

Incredible, right???  Finally.  A drug which can potentially affect the blood brain barrier!
Perfuza (toxicmuzab) may be the greatest money-making MS drug in history.
Projections are now at 2-3 billion for 2018 alone.


Only kidding.

The paper I'm quoting from, verbatim, is the recent JAMA review of angioplasty for CCSVI from the Brave Dreams clinical trial. 

Just replace my made up block buster drug Perfuza (toxicmuzab) with angioplasty to restore venous flow.   And then, write a conclusion and snarky editorial that says that we should not pursue this treatment any further, and that CCSVI research is over.

Even though the conclusion of the paper says that over half of patients saw benefit in cerebral blood flow from CCSVI treatment.

The editorial which goes along with this publication is actually incorrect.  The author of the editorial, Dr. Ari Green***, claims that there was absolutely no benefit in those treated for CCSVI, that there was no reduction in new lesions.  Here, read the editorial for yourselves, and read the paper again, and tell me---isn't this incorrect?
https://jamanetwork.com/journals/jamaneurology/fullarticle/2664000

***Dr. Green has received personal compensation for activities with Inception Sciences, Mylan Pharma, Medimmune, and Bionure. Dr. Green has received personal compensation for serving on the board of Inception Sciences. Dr. Green holds stock and/or stock options in Inception Sciences. Dr. Green has received research support from Inception Sciences, Biogen, and Novartis.  link
Dr. Green's Inception Sciences Company owns the patent for an antihistamine-like molecule thought to remyelinate neurons. I wrote about the absurd hype regarding a 1.3% improvement in visual acuity here:  link

To recap---this published paper from the neurologists of the Brave Dreams trial just proved, conclusively-
1. CCSVI is a real condition in people with MS.
2. There are a variety of venous malformations.  There were patients with closed jugular valves, refluxing blood flow, and hypoperfusion.
3. Venoplasty was able to restore normal flow in 54% of the patients.  Not all malformations can be treated with PTA alone.
4.  63% of treated patients had no new MS lesions on MRI at 12 months.
Doesn't this count for something?  At least additional study?

What is real news? What is fake news?
Is this simply spin or is it something darker?

If a room full of neurologists look at the results from CCSVI venoplasty and conclude 
"The delayed effect of venous PTA 6 months after the procedure on the magnetic resonance biomarker suggests a possibility that PTA may produce benefit for a subgroup of patients with MS. This should be further analyzed and investigated." 

yet still write a conclusion and editorial suggesting CCSVI research be stopped--- what is reality?

Please, tell me.  Honestly, I'm flummoxed.

More ahead.
Joan

MS Vascular Research Round Up

I wanted to do a summary post on the most recent research into the vascular connection to Multiple Sclerosis, prior to Dr. Zamboni's presentation at the Veith Conference in New York City this Saturday.   CCSVI Alliance will be hosting a patient friendly "Facebook Live Event" on November 18th with Dr. Zamboni.  Link to Facebook Event Page

Since Dr. Zamboni first published his pilot study in 2008 of MS patients treated with venoplasty to relieve slowed venous drainage, or a condition he named Chronic Cerebrospinal Venous Insufficiency,  the landscape of neuroscience has changed drastically.

In fact, we now know that the brain has a cleansing system connected to the peripheral lymphatic system, which depends on timely and efficient drainage.  

Here's a BBC radio presentation on the importance of the newly discovered Brain's Drain.
link
As the science reporter states in this interview,
"Making sure a drainage system is flowing properly could be really important for the health of the brain."

We are learning more about how the brain clears proteins, metabolites, immune cells and waste---while awake and asleep.  The jugular veins are the major collection area for this process--as this is where the brain's lymph, CSF and deoxygenated blood converge.   link

If researchers want to investigate a method of action (MOA) as to how venoplasty to relieve slowed venous drainage and repair of jugular defects has helped people with MS, they might consider the following:

1.  Corroboration of the brain's lymphatic system in humans.

NIH researchers find lymphatic vessels in humans, and confirm prior research from the Kipnis Lab at University of Virginia.

To confirm that the vessels were lymphatic vessels, the team used a dye that’s too big to leak out of blood vessels. MRI scans from two subjects with this dye showed brightly lit blood vessels in the dura, but not the suspected lymphatic vessels. These results suggested that the first dye leaked out of the blood vessels into surrounding lymphatic vessels.

The researchers also looked at the suspected lymphatic vessels in autopsied human and monkey brain tissue. They found that the vessels contained specific cells and protein markers that are unique to lymphatic vessels and distinguished them from blood vessels. These findings suggest the lymphatic system is a common feature of mammalian brains.

“We literally watched people’s brains drain fluid into these vessels,” Reich says. “We hope that our results provide new insights to a variety of neurological disorders.”

“These results could fundamentally change the way we think about how the brain and immune system interrelate,” says NINDS Director Dr. Walter J. Koroshetz
.link

2.  Fibrinogen, a blood clotting protein, initiates myelin loss and inhibits remyelination in MS.

The Gladstone Lab confirms that all it takes to initiate demyelination in the brain is a drop of blood on brain tissue.  The clotting protein, fibrinogen, which increases when the coagulation cascade is initiated during a break in the blood brain barrier, is highly destructive to myelin.  Not only does fibrinogen damage myelin, it blocks the body's stem cell mechanism of myelin repair.

If the brain is unable to drain in a timely and efficient manner, venous hypertension and small breaks in the blood brain barrier may occur.  These cerebral microbleeds have been documented on 7T MRI in MS patients.

Akassoglou has spent much of her career studying the role of the blood-brain barrier and fibrinogen in neurological diseases. She previously showed that when blood leaks into the brain, fibrinogen causes inflammation by acting in brain immune cells, which can lead to brain damage.

In the new study, Akassoglou and her team uncovered another, yet unexpected effect of blood leaking into the brain.

“We found that fibrinogen stops adult stem cells from transforming into the mature cells that produce myelin,” explained first author of the study Mark Petersen, MD, a visiting scientist in Akassoglou’s laboratory and an assistant adjunct professor of pediatrics at UCSF. “This blockade could be harmful for regeneration in the brain.”  link

3.  M (motion) Mode ultrasound shows a higher rate of jugular valve irregularities in people with MS, compared to healthy controls.

Researchers noted, using motion mode ultrasound which visualizes blood flow and valve activity, that more people with MS (82%) have fixed, or immobile jugular vein valves.  98% of healthy controls had jugular valves which opened and closed with blood flow.  This created brain outflow abnormalities.     link

4.  Endothelial cells are the interface between lymphatic, immune and vascular system of the CNS.

Researchers are probing further into the importance of vascular endothelial cell health, in light of the new discovery of brain's lymphatic network.

The lymphatic network linking the CNS to draining lymph nodes may contribute to the inflammatory reaction occurring in multiple sclerosis (MS). The abundance and strategic positioning of endothelial cells at the blood-brain barrier level most likely endow them with an important role in controlling local adaptive immune responses, rendering them potential therapeutic targets in neuro-inflammatory such as MS.
link

Disruption of the blood–brain barrier (BBB) is a defining and early feature of multiple sclerosis (MS) that directly damages the central nervous system (CNS), promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis.  link

5.  People with MS have cervical lymph nodes which are twice the size of normal people, whether or not they are on immune modulating MS drugs. 

As the cervical lymph nodes are the collection area for the brain's newly discovered lymphatic system, and these nodes drain into the junction of the jugular and subclavian veins, this anomoly needs to be further investigated.

Cervical lymph nodes are the first drainage stations of the brain and therefore play a key role in neuroinflammatory disorders such as multiple sclerosis.  The abnormalities shown by ultrasound in cervical lymph nodes are related to deep ones and independent of the ongoing treatment, suggesting a relationship between lymphatic drainage and disease pathology.  link


As we can all see, understanding the vascular connection to MS is now expanding in research labs around the globe.  The era of the EAE mouse model of MS as an auto-immune disease is being replaced by an understanding of MS as an inflammatory disease related to cerebral perfusion, the vascular endothelium and lymph system.
And yes, venous function remains integral to this understanding.

Onward,

Joan

Setting the record straight

I want to simply state some facts for my readers.  Because if I don't, journalists and bloggers will continue to create a narrative of the kooky singing wife, who found some crazy researcher online and led the world on a goose chase.  And that's not true.  And it's really hurtful.

Some factual, documented history:

1.  I believed there was a vascular connection to my husband's MS diagnosis from day one.  That would be March 23, 2007, the day we got his serum results from the doctor and I saw so many numbers that were way out of normal range.   Coincidently, my birthday.

2.  Using Jeff's serum results as a point of reference, I went to the library and took out every single book they had on MS, including McAlpine's history of Multiple Sclerosis--which had a section on the long history of the vascular connection.  This is where I first read about Dr. Tracy Putnam.  link The pile of textbooks also included Dr. Swank's research.  Dr. Swank wrote about the connection of MS to the blood.  He published over 100 research papers on MS.  He wrote about capillary fragility, petechiae and hypercoagulation in his MS patients--all of this research rang a lot of bells for me.  link

3.  I was on a forum called "This is MS" in September 2007.  I wrote about Jeff's serum results, hypercoagulation, and postulated on a bunch of research with other people with MS and caretakers.  It was a great community, and we shared papers, programs and MS research.

4.  Using pubmed and my local library, I eventually came to the intersection between the vascular and immune system I had been searching for---the endothelium.  Using published and peer-reviewed science, I created The Endothelial Health Program for Jeff and shared it on This is MS in the summer of 2008.   I saw a connection between many of his vascular issues (petechiae, high Crp levels, hypercoagulation, high liver enzymes), endothelial dysfunction, and his MS diagnosis.  We found that by changing his diet to a Swank program, increasing his Vitamin D levels, including cardiovascular exercise, thinning his blood with proleolytic enzymes, getting him out in sunshine, reducing work stress, improving his sleep---he was doing much better, he did not have a relapse and his serum results normalized. http://ccsvi.org/index.php/helping-myself/endothelial-health

5.  I wrote to endothelial researchers at USC and Stanford, asking if they had any knowledge of studies or published research on the function of the endothelium in MS.  Both of them e-mailed me back.   I began a correspondence with the researcher at Stanford, because he was the most interested in this connection.  Here is part of his reply.  I have all of the e-mails, if anyone aside from me ever truly wants to get this story correct.

"I enjoyed reading your treatise. 
I quite like the hypothesis that MS is secondary to a derangement of the endothelium of the cerebrovasculature, that results in inflammation and local damage. 
I am also in agreement with your contention that a functioning endothelium is a major key to health. 
Furthermore, I agree that diet and exercise are critical for endothelial health." 

6.  It would be three months later I would send more research to this doctor.  One of the papers was Dr. Zamboni's new publication on CCSVI, which had been shared with me, the "vascular hypothesis gal" on This Is MS.   He was fascinated by the research, and suggested further testing for Jeff.  Here's part of that e-mail.

  "You could get more evidence for cerebral venous abnormalities (I would be particularly concerned about venous stenoses) by MR imaging, with attention to the cerebral veins. "

7.  We would eventually bring Jeff up to Stanford for TESTING to see if he had any venous abnormalities.  It took a few months to schedule, as he was busy composing and we needed to travel from LA to the Bay Area.   He was tested in April, 2009.   My mistake was that I wrote about all of this online, on the This is MS forum.  I should not have done this.  It is my one, deep regret.  But it is also why I continue to blog and write.  Because I feel hugely responsible for what would later happen.

8.   Jeff had serious venous abnormalities, documented on MRV.  link  He had a 99% stenosis in his left jugular vein and an 80% closure of his right.  The doctor we were consulting with felt this was a serious issue for his brain perfusion, and suggested we think about potential treatment.  We went home.

9.  After consulting with other physicians,  Jeff scheduled his venoplasty treatment for May 2009.  He went back up to Stanford and was treated for his venous abnormalities.  He had a profound response on the table---he felt as though the "lights came on" after a stent was opened on his left side.   He came home and slept soundly, without spasms, for the first time in over a year.  He was dreaming again.  He also had a terrible headache the first day, and would develop severe shoulder pain from having his accessory nerve pinched by stents.  These side effects from the treatment would pass, but it was scary.  Again, I wrote about it online.

10.  People read what I wrote, called Stanford, were treated there or tried to get treated elsewhere.  The press picked it up, and the rest is pretty well documented.  What is never reported correctly is that I didn't force an IR to treat Jeff.   We asked him to TEST Jeff for venous abnormalities.  When we saw how bad they were, the IR suggested treatment,  and we eventually agreed.

I never called venoplasty a cure for MS.  I also never meant for people to get hurt, or travel for medical tourism, spend thousands of dollars (as Jeff was covered by our insurance)  or most terribly, to die from complications.  I certainly didn't want to be labeled the crazed wife who forced an IR to treat her husband.  I always said this was only part of living a vascularly healthy life, to encourage healing and strengthen the heart-brain connection.  I never used the word cure.   I started the Facebook group because I was really concerned with how this research was being discussed as a cure.    link  I was also shocked with how vehemently the MS specialists were denying any link to the vasculature.  I wanted people to know this was only a treatment, and it might not be right for them. Which is partially why I stayed online.   That, and a huge amount of pride, I'm sure.  Ego is never a good thing, and I know it complicated this issue.

But in all honesty, all I wanted were answers for the love of my life.  And we hung around because we had hoped this could be helpful to others.  But to be continually portrayed as cure seekers, zealots and wingnuts by the NY Times, the Wall Street Journal, and other publications (which will live online ad infinitum) and to have our names linked to false and incomplete reporting is simply too much.

So, there it is.

Going for a walk with my love, and our 17 yr. old dog, Angel (another medical anomaly)
Have a nice day,

Joan

An OTC antihistamine drug remyelinates? Really?

Time to get the facts behind the headlines-- as I've seen lots of online reporting regarding a new study out of UCSF on the OTC antihistamine clemastine fumarate and potential remyelination in MS. link

I've been following this research since it was first presented at AAN conference in 2016. link There was a lot of hype then, and I remember reading the paper and thinking, really? What's the big deal? As we dig further into the study, we learn that there never was any proof of remyelination---this is just a guess on method of action. They didn't actually see any new myelin on brain lesions, they didn't see any evidence of myelination on MRI. So what did they see? There was a very small, almost insignificant, improvement in eye response, using visual evoked potential measurements. (here's how this test works. link )

To be included in the study, participants had to have a delay in transmission time beyond 118 milliseconds in at least one eye. During the study, delays were reduced by an average of 1.7 milliseconds in each eye per patient among those who received the antihistamine.
Wow. That's a 1.4% average improvement. Certainly not a resounding success.
It's also not possible to state this improvement is due to remyelination--

One of the biggest difficulties in the development of remyelination therapies for MS is the demonstration of remyelination in living patients. Indirect measures, such as improvements in neurophysiological outcomes, such as electroencephalography, evoked potentials, optical coherence tomography, and transcranial magnetic stimulation may suggest, yet not confirm, remyelination (144–148). Functional improvements could indicate remyelination, but could also indicate neuronal plasticity or the spreading of sodium channels into demyelinated internodes, which could also restore conduction in unmyelinated axons (144, 149, 150) link

And my thought on the potential method of action?

The anti-histamine might actually be reducing endothelial cell permeability, by blocking the histamine receptor. The method of action would be on the vascular endothelium. Which makes sense to me. Even still, it’s not much. link

Another issue---the major side effect of FATIGUE was reported by most who took the antihistimine. More fatigue? For people with MS? Jeff laughs at this….no way. Not worth it. He won’t take an antihistimine if he has an allergic reaction (cat or pollen), for the same reason.

The claim of remyelination and “reversal of MS” is pure conjecture and market hype BS.
Want an OTC supplement that has better results and won't leave you fatigued?

EGCG (green tea) has as good or better results in VEP, less side effects. Of course, it is harder to make money for drug companies, since you can't patent green tea. link

Here's what the trial investigator claims---

“To the best of our knowledge this is the first time a therapy has been able to reverse deficits caused by MS. It’s not a cure, but it’s a first step towards restoring brain function to the millions who are affected by this chronic, debilitating disease,” said the trial’s principal investigator, Ari Green, MD, also Debbie and Andy Rachleff Distinguished Professor of Neurology, chief of the Division of Neuroinflammation and Glial Biology, and medical director of the UCSF Multiple Sclerosis and Neuroinflammation Center.

I would challenge his assertion, and say his knowledge might not be the best. You know what proves myelin repair? Actual remyelination of lesions shown on MRI, a reversal of brain atrophy and lack of MS progression. That's what Jeff has had since venoplasty treatment and following the Endothelial Health Program. And we have proof on MRI. link

Here's the research and science behind aspects of Jeff's program--which shows actual remyelination:

Vitamin D link
The brain's plasticity link
Exercise link
Colorful fruits and vegetables, full of antioxidants. link

Read past the headlines, friends.
And be well,

Joan

Interferon β almost doubles the risk of stroke and migraine in MS. Why?

An important observational study on long term use of interferon β and increased risk of stroke and migraine in MS was just published by one of my favorite MS researchers, Professor Helen Tremlett at the University of British Columbia.  Current interferon beta drugs prescribed for MS are Avonex, Betaseron, and Rebif.  

The complete paper is available here:
Evaluating the Safety of B Interferons in MS

Dr. Tremlett does not represent any drug company or MS treatment.  Dr. Tremlett simply studies people with MS, to understand disease progression and environmental factors, like gut microbia, vascular commorbidities, liver enzymes, Vitamin D, sun exposure, fatigue and pregnancy.  link

She has been studying the adverse affects of MS drugs and documenting many things pharmaceutical trials marginalize, or completely ignore.  In her publications, she highlights MS DMDs' modest efficacy, and the fact that clinical trials are of short duration and in a highly selected patient group, and do not give us a complete picture of long-term adverse events.

The IFN-βs are modestly effective, reducing relapse rates by about one-third and having a beneficial effect on imaging outcomes,² but findings regarding longer-term effects on disability have been mixed.^3,4The IFN-βs are generally considered safe, especially compared to newer agents for MS.⁵ However, few studies have systematically assessed their safety in real-world clinical practice (appendix e-1 at Neurology.org).⁵ A meta-analysis of 9 clinical trials estimated that patients treated with IFN-β had a 2.8-fold increased risk of discontinuing drug because of an adverse event compared to the placebo group. The most common adverse events were flu-like symptoms, injection-site reactions, leukopenia, lymphopenia, and elevated liver enzymes.⁶ However, because of their short duration and relatively small sample sizes, clinical trials cannot identify all potential adverse effects of a drug treatment or predict the safety of the drug in clinical practice. Furthermore, participants in clinical trials are highly selected in terms of comorbidities and concomitant medications and often differ substantially from patients who use the drug once it reaches the market. We identified signals of potential adverse events related to IFN-β treatment in a large population-based cohort of patients with RRMS.

This new study looked at patients with RRMS, registered at the UBC MS Clinic from 1995-2004, who were treated with interferons.  2,485 eligible patients were followed up until death, until they left BC, or until they stopped taking interferons.  After compiling the data, the study showed that patients who had taken interferons, there was a 1.8 fold increase (almost double risk at 180%) of stroke or migraine.  There was also a 1.3 fold increase in depression and hematologic abnormalities.

I realize this might be an obvious observation to many of my readers, but I feel like it will be overlooked by neurologists.  All of these adverse affects are vascular.  Stroke, migraine, blood issues --and yes, even depression---are related to blood flow, cerebral perfusion, coagulation and endothelial health.  Interferon B changes platelet adhesion to the endothelium and appears to raise blood pressure.

Here's more on this from the paper:

Our study is a comprehensive assessment of the potential risks for a broad range of adverse events related to IFN-β in the real-world clinical setting. Several of the adverse events that we observed to be associated with IFN-β exposure such as migraine, hematologic abnormalities, and depression are included in the known safety profile of the IFN-βs. Stroke, on the other hand, is not well recognized as a potential adverse event, being limited to a few case reports.^19,20 Nonetheless, it is biologically plausible that this event is associated with IFN-β because this drug may alter wall competence or enhance the major histocompatibility complex-1 molecule expression of platelets and other cells,^21,22 resulting in enhanced platelet adhesion to the endothelium.^22,23 
Hypertension can also increase the risk of both migraine³⁵ and stroke, and we observed a higher risk for hypertension among current users of IFN-β, which might point to a common pathway.


Other researchers are also studying the long term vascular side effects caused by interferons---
including thrombotic microangiopathy, which is a disease of endothelial injury resulting in thrombosis.  These clots can cause stroke, chronic kidney disease and renal failure.  
link
link

Also being studied is how interferons affect blood clotting and cause hypertension
link

There have been case studies where people with MS who were treated with interferon B had subsequent strokes.
link
link

Previous studies have shown that people with MS already have a two fold increase in risk of venous clots, independent of drug treatment.
link

Perhaps long-term use of Interferon β-- which further increases the risks of clotting, hypertension,  stroke and endothelial dysfunction, while only reducing relapse risk by 1/3-- isn't the best approach for people with MS.

The vascular connection to MS is real.
Endothelial health is essential.

Joan

Caution and concern: minocycline and antibiotics for MS

There are new reports and publications advocating for use of minocycline as a "safe and inexpensive treatment for MS"--as well as a new publication on combined antibiotic treatment for CCSVI.

There is no doubt that antibiotics have been helpful for many with MS.

However, I have serious concerns about using antiobiotics as an MS treatment, due to a side effect which can go undetected, causing damage to the brain and vision.

First, a bit of history.  When Jeff was diagnosed with MS in 2007, I found a publication which considered use of minocycline as a low-risk MS treatment.  Yes, this antibiotic has been touted before.  What's old is new.  link

I brought in the research in and asked his neurologist if she would prescribe the antiobiotic for him, and she agreed.

Jeff took minocycline for a couple of days, and developed serious pressure headaches.  He kept on with it, even though he was in agony,  as we had read some articles about "herxing" and bacterial "die-off" and thought maybe that might be the issue.  But the headaches got worse.  After consulting with his neurologist, we learned that Jeff's headaches were most likely due to a KNOWN side-effect of minocycline.

Minocycline is believed to hamper reabsorption of cerebrospinal fluid in the brain,  potentially creating intracranial hypertension and vision loss.  In fact, doctors know about this side effect, and it has been well documented.   For someone with already slowed venous flow and build-up of CSF (as a patient with CCSVI),  this side effect could be even more harmful.

As intracranial hypertension does not always manifest in vision loss or headache, it might be difficult to know if this antibiotic is hampering CSF flow in the brain.   link
For those who wish to learn more about how all tetracyclines, like minocycline, create intracranial hypertension. link

Jeff's neurologist advised him to stop taking minocycline, and the headaches went away.  He was lucky, he had a very obvious side effect, and knew to stop.  But not everyone gets headaches.

So, please be careful.  Something which seems "benign" as a treatment for MS, may actually have side effects that we still do not understand.

We also do not clearly know the impact of antibiotics on the gut's microbiome.  And this is another area of concern for me.

The study, recently published in mBio, found that just one weeklong course of antibiotics changed participants' gut microbiomes, with the effects sometimes lasting as long as a year. After all, antibiotics don’t discriminate—as they attack the bad bacteria, the good ones are vulnerable too.
link

For people who have benefitted from antiobiotic protocols, I'm truly happy for you!  MS is indeed a snowflake disease, and chronic infections are known endothelial disrupters.   This post is for the folks who have not had benefit, or had damage, or who want to know more.

Because people with MS do not always get the complete story,
Joan

Jugular anomalies and collateral flow in multiple sclerosis

There is a new paper recently published in the American Journal of Radiology from Dr. Haacke's superb radiology team at Wayne State University in Detroit, called Jugular Anomalies in Multiple Sclerosis are Associated with Increased Collateral Venous Flow

The complete paper is here:  link

As many of my readers know, there has been very little study of the outgoing venous system, especially when compared to the ingoing arterial side of blood flow.  We have a well-documented understanding of how problems with carotid arteries, the main inflowing blood vessels to the brain, can cause disease.  link  There are many papers on carotid arterial stenosis and stroke, dementia, Alzheimer's and other diseases of neurodegeneration.  And carotid artery scans are quite commonplace.  Angioplasty treatment for carotid arterial disease is an accepted and even routine practice today.

But in contrast, the venous system, specifically the internal jugular veins which are the main drainage route for the brain, has been under-researched and is not well understood.  A common thought from doctors has been that the brain can utilize collateral veins to drain, and that when the jugular veins are blocked, it's no big deal, since there are other veins to take up the flow.  This paper is one of the first which is looking specifically at how blockage of the IJV changes venous flow patterns.

Research on venous abnormalities in MS thus far has been limited to the IJV, and little is known about extracranial venous collateralization. The extrajugular drainage system consists of the vertebral venous system; the deep cervical veins, which anatomically are paraspinal toward the heart; and the anterior and external jugular veins, which receive blood from facial and superficial areas.8 Although the presence and structure of collateral veins have been assessed by using time-resolved imaging of contrast kinetics venography, flow values were not quantitatively evaluated.9-11 The purpose of this work was to examine the relation of extracranial venous anatomy and flow in a large cohort of patients with MS and healthy controls (HCs) taken from our neuroimaging data base.12 Because of the complexity of the extracranial venous system, we have classified these vessels into 3 groups based on anatomic MR information and their drainage path: primary (ie, IJV), paraspinal, and superficial. We hypothesized that increased venous paraspinal and superficial flow will also be observed for cases that evidence abnormal IJV structure and flow. In contrast, a subset of patients with MS may have a distinct collateral venous flow pattern compared with patients with MS and HCs without structural venous anomalies. 

In a study of 153 people with MS, 55% of the MS group exhibited jugular venous stenosis.  In the healthy control group of 105 people, 20% had stenotic veins.  Both of these groups had collateral venous flow, either through the vertebral or paraspinal veins.   The anatomic assessment of these vessels really isn't the complete picture.  Remember Dr. Zamboni's quote--"It's not the architecture, it's the flow."

Collateral flow has hemodynamic consequences.   This collateral system is like taking a winding country road when the main highway is blocked.  It is slower, less direct and has consequences for the brain, including venous hypertension and venous insufficiency.  There will be further research on the hemodynamic consequences of collateral venous flow.

One of the leading researchers publishing on this link is ISNVD member Professor Clive Beggs.

Professor Beggs has been able to show that MS is associated with changes in the dynamics of the CSF pulse in the cranium, and that the normal relationship between this and the jugular veins is profoundly altered in MS patients. He has also found that venous drainage anomalies in patients with Alzheimer's disease are associated with blood retention in the cerebral veins, suggesting that constricted venous outflow might be a generic phenomenon implicated in the pathophysiology of other neurological diseases.   Professor Beggs said: “My work suggests that vascular anomalies can profoundly alter the biomechanics of the intracranial space. This is important because there is a growing body of evidence that altered haemodynamics in the cranium are associated with a wide range of neurological conditions.  link

I know it has been frustrating for those waiting for CCSVI science to come in.  In the ten years since Dr. Zamboni first published his initial papers on CCSVI, we have seen an unprecedented pushback from the neurological community to even consider venous flow and the brain.

But we have also seen new publications like this one from radiologists,  and contributions from groups like the Nedergaard Lab, the Kipnis Lab, the Gladstone Lab and the ISNVD.  These groups are publishing on the newly discovered lymphatic system, which relies on the venous system of the brain.  We are now seeing how absolutely vital the brain's veins are--and how problems in venous flow are linked to all diseases of neurodegeneration.  This is real, and the science is coming in.  link

For those who are "out of wait" and frustrated by the pace of this research--it is best to consider the vascular connection to MS and live your most  endothelially healthy life today.  Talk to your own doctor about eating whole, colorful natural foods, exercising or physical therapy, getting UV ray exposure,  increasing quality sleep, reducing stress,  and finding joy and community.  Maybe consider NUCCA or atlas orthogonal treatments, having your venous system scanned for irregularities and getting treatment from a respected IR.

Be hopeful, and be well.
Joan

My husband's MRV from Stanford University, April 2009
Showing 99% and 70% obstructed IJVs and collateral flow (those curly, small veins) before his venoplasty treatment

MS is vascular

MS is caused by a breakdown of cerebral endothelial cells.  The loss of these vascular cells, which line all 60,000 miles of our blood and lymph vessels, is why the blood brain barrier becomes open, how immune cells are called in creating inflammation, why the coagulation cascade occurs increasing fibrinogen, what allows for death of neurons,  what causes MS to progress.

For those who hate medical language, find it confusing, and like easy to understand explanations, I wrote up a simple post on the endothelium and how it works here:  link

I'm not the only one saying the endothelium is central to MS.

A new paper, edited by MS neurologist Lawrence Steinman at Stanford University states the following:

Endothelial cells (ECs) in the CNS form a unique blood–brain barrier (BBB) that is broken down in multiple sclerosis (MS). New therapies are sorely needed to restore BBB function in this disease.

Disruption of the blood–brain barrier (BBB) is a defining and early feature of multiple sclerosis (MS) that directly damages the central nervous system (CNS), promotes immune cell infiltration, and influences clinical outcomes. There is an urgent need for new therapies to protect and restore BBB function, either by strengthening endothelial tight junctions or suppressing endothelial vesicular transcytosis.

This paper is a collaborative review from Columbia University, UC Irvine, Stanford and the Albert Einstein College of Medicine.  You can read the abstract here:
link

I really don't know how else to say it.  Your endothelium is important.  I've been blogging about this scientific reality since my first post on this blog.  Hundreds of my posts are about endothelial cells, why they are important, why they die, how to maintain them.  Obviously, I didn't do the research, I just put it together.  

Yes, I am gratified that universities acknowledge the importance of the endothelium in MS.  But so much of this remains a continued search for industry funding and "pharmacologic enhancement" rather than a search for the etiology, or cause of MS.  Or an understanding of how the endothelium is damaged by a variety of lifestyle, vascular and disease factors.  

I wanted to understand how to protect and strenghten the endothelium, which is why I originally contacted Dr. John Cooke, a researcher at Stanford University who had published a book on nitric oxide and lifestyle measures to heal the endothelium in cardiovascular disease.  He is now at Houston Methodist, heading up a lab which is creating endothelial cells from stem cells, for use in regenerative medicine.  He's getting there!  link

Below are the interventions we discussed, which I compiled for Jeff and others with MS.  The endothelium can heal by using these strategies.   Jeff has done really, really well following this program.  I have also heard from other people with MS who are employing these measures, and finding health and stability.  Please talk to your own doctors before beginning any lifestyle program, to make sure it is right for you.  I am not a doctor.  But I trust people like Dr. Cooke.
http://ccsvi.org/index.php/helping-myself/endothelial-health

The International Society for Neurovascular Disease recently had their 7th annual conference.  This year, the President of the ISNVD was Dr. Stephen Alexander.  I originally met Dr. Alexander online and later in person at the first meeting of the group which would become the ISNVD, back in 2009 in Bologna, Italy.   Dr. Alexander is an endothelial researcher who studies endothelial cells in MS and inflammation.  He and his fellow researcher, Dr.  Alireza Minagar, have published many papers on the vascular connection to MS.

This is their paper, which caught my attention ten years ago:
Multiple Sclerosis as a Vascular Disease


Their most recent effort is a chapter included in the book "Inflammatory Disorders of the Nervous System" called "Emerging Roles of Endothelial Cells in Multiple Sclerosis Pathophysiology and Therapy"

The complex pathogenesis of MS can only be appreciated when and if vascular contributions are recognized as a significant part of MS etiology. Indeed, many novel therapies for MS target the mechanistically relevant vascular inflammatory features of these conditions and implicate cerebrovascular endothelial cells (CECs) as the “failing gatekeeper” of the blood-brain barrier (BBB).    link


And yes, CCSVI is a factor.  When blood flow is disturbed, due to venous hypertension or stenotic blood vessels,  there is a lack of shear stress over endothelial cells, and they die.  Endothelial cells need constant moving blood.  Here is a paper from Dr. Alexander on Venous Endothelial Injury in Diseases of the CNS.   https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-11-219

While researchers continue to put together the pieces and find pharmacological means to strengthen the endothelium, there are things you can do today to help yourself.

I know, I repeat myself.  A lot.  Because this is important.

Heal the endothelium, heal the vasculature, heal the body.

Joan





The brain’s blood vessels are lined with endothelial cells that are wedged tightly together, creating a nearly impermeable boundary between the brain and bloodstream.

The Endoplasmic Reticulum (ER), Rab32 and MS

Once again, the medical news headlines are full of "breakthrough!" "cause of MS!" "new way of looking at the disease!" and even "Cure!"
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Researchers in the UK and Canada have found the protein Rab32 appears in large quantities in autopsied brain tissue of those who had MS.  Higher levels of this protein cause a disruption of communication between cells, and lead to mitochondrial malfunction and neurodegeneration.  Researchers say they do not know what causes this increase in Rab32, but they believe that by inhibiting this protein with new treatments,  they can slow MS progression.  However, neurovascular researchers have been studying this mechanism for many years in Alzheimer's, ALS, Parkinson's and dementia---and vascular researchers know why this happens (keep reading.)
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I find it's always a good idea to read the actual research, rather than rely on click bait or fake news headlines.  Many medical reporters have only a basic understanding of science.  The researchers who send out press releases like to keep it that way. The news stories continue to mention the autoimmune theory of MS right at the start, yet this new discovery has little to do with autoimmune disease, and almost everything to do with inflammation of the vasculature and endothelial dysfunction.

Here is the complete paper:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260063/

Together, using multiple patient tissue samples, our findings indicate that Rab32 increases dramatically in neurons and macrophages/microglia localized within active MS lesions and that high amounts of Rab32 coincide with the expression of CHOP. In contrast, chronic MS lesions show Rab32 predominantly in neurons.

Simmen and his colleagues were quick to note that it’s not yet clear what actually causes the surge of Rab32. They also note that Rab32 is likely not the only important protein when it comes to unraveling the mystery of MS.
“Rab32 is just one of the proteins that is having the effect of drawing the ER and mitochondria too close. There are dozens of other possibilities,” he said.
link


So,  as we learn when digging a bit deeper into the research, it's not just about the increase of Rab32.  This just makes a great headline, and will fund ongoing research for these labs.  But there are other unfolded proteins causing cellular disruption.

At the center of this "discovery" is the endoplasmic reticulum (ER) and ER stress.  The ER is a membraneous structure of a cell, it connects to the nucleus and provides a protective and cleansing function.  Red blood cells do not have ERs...but the liver or pancreas cells have lots of them.  So does the brain.  This is because the ER allows for protein synthesis. And we've known about ER stress in other disease for quite a while.  So, to catagorize this as a "discovery" is not really true.  It's just new for MS researchers to look at how ER stress is linked in Rab32 increases in the MS brain.

The link of ER stress and neurodegeneration is not new.
The ER stress-associated cell death pathways have been recognized in the numerous pathophysiological conditions, such as diabetes, hypoxia, ischemia/reperfusion injury, and neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and bipolar disorder.
link

Under various pathological conditions, the perturbation of any of the three physiological functions of the ER results in so-called ER stress and can lead to an accumulation of the newly synthesized unfolded and misfolded proteins in the ER. Among the stimuli that promote ER stress are ischemia, inflammation, and disorders that impair the ER’s ability to properly fold polypeptides or eliminate unfolded proteins (11).
link

Thanks to the work of vascular researchers, we know a few things which can create ER stress.  I suggest reading this complete paper.  link
But to summarize:

ER Stress, Endothelial Dysfunction and unfolded protein response are caused by:
1. High levels of homocysteine
2. Disturbed blood flow and lack of good shear stress
3. High levels of bad cholesterol (LDL) and low levels of good cholesterol (HDL)
4. High levels of glucose
5. High blood pressure and obesity

All the stuff mentioned in the Endothelial Health Program.
link
There are things you can do today to improve health and reduce ER stress.

A final thought for blog readers---targeting one misfolded or rogue protein without considering the mechanism which leads to this perturbation may not be the most successful approach. This is my main concern, and why I wrote this post. We have learned this through years of Alzheimer's research and treatment targeting the beta amyloid protein, which still has no success in alleviating the disease process. In contrast, a multimodal lifestyle approach employed at UCLA led to Alzheimer's disease reversal. link

Big picture: why do cerebral hypoperfusion, cerebral endothelial cell aptosis, a breakdown of the blood brain barrier, ER stress and neurodegeneration occur? 

Continue to dig deeper, past the MS News headlines.
There is truth beneath all of the hyperbole.

Joan

Fast Mimicking Diet (FMD) for MS

In the name of research, and with a bit of curiosity,  I tried a fast.   I've recenly completed the ProLon Fast Mimicking Diet.    More details about the specifics later, but first, you may well be asking---why would someone who LOVES food (yes, a lot link) voluntarily go on a five day fast?   Believe me, I asked myself the same question.

Honestly, I wanted to check out the program before sharing more research with you all.  I really think this is an interesting approach for MS, as it potentially reduces inflammation, boosts cellular rejuvenation, and resets the immune system.  This program has had great success for patients with diabetes and cancer, as well.  It's beginnings were in anti-aging therapies, and clinical trials in many chronic conditions related to aging are ongoing.

Fasting is not something people with MS should do without a doctor's supervision.   I had to get approval from the ProLon nurse (over the phone) before starting the program---and I'm healthy.  People with MS will need even further approval from their doctors, which is a really good thing.  But it might be worth exploring.  You can take the research and links to your doctor and see if this might be right for you.   Jeff said he's interested after watching me last week, so we'll clear it with his doctor and do it together later this year.

Here's the science.  In 2016, a study at the University of Southern California researched fasting and multiple sclerosis, and found that caloric reduction with a fast mimicking diet (FMD) did all sorts of wonderful things for the body, which specifically helped those with MS.

The USC study in mice with EAE and humans with MS found that a fast mimicking diet (FMD) made the body produce more of the hormone corticosterone, which in turn killed off damaging and inflammatory immune cells, and led to a production of new, healthy stem cells.  This study also saw regeneration in myelin producing cells, and reduction of MS symptoms.  All amazing stuff!  Here's more on his study in layman's terms   link    Here is the complete paper, which I suggest reading, and sharing with your doctor if you're interested.    Cell Reports FMD in MS publication

It's potentially an affordable alternative treatment for MS --so get ready for pharma to try and take it down with their own "trials" ( link to "Pragmatic Trial" of fasting with Tysabri )  You know something is worthwhile when pharma gets involved in debunking.

The lead USC researcher, Dr. Valter Longo, also discovered that fasting does not necessitate complete avoidance of food, but a fasting state can be reached by restricting caloric intake in a specific manner.  Thus the "fast mimicking" part.   This is something which might be easier for most of us to accomplish, and this was a key point for me.  I could never do a liquid fast.  I simply get too light headed and tired from low blood sugar.  But I found this program to be much different, and very doable.

I'd had some nice back and forth e-mails with Dr. Longo when this research was first published last year.  We both share a love of music and medicine.  He was a young music student in Italy before coming to the states to study jazz guitar.  He became interested in the study of aging, and got his PhD in biochemistry at UCLA, then joined the USC Davis School of Gerontology.  He is also Director of the USC Longevity Institute.  His focus is on how caloric restriction and fasting kills damaging cells while inducing healthy stem cell production.    link to Dr. Longo's story

I had wondered if any of his FMD studies had looked at markers of inflammation related to endothelial improvements.  I had found prior research looking at this connection.  link  He replied that his group wasn't looking at that specific aspect. He felt that the benefit of FMD was more about reduction of damaging autoimmune cells and a rejuvination of stem cells. But I have a hunch the increase in cortisone is also helping strengthen endothelial cells and reduce cell permeability--as well as helping the microbiome.   The FMD has been shown to reduce C reactive protein in other studies, so there is a vascular connection. I hope more research will be done on these other aspects of the program.

Since I wanted to remain impartial in my analysis of Dr. Longo's FMD, I didn't ask him for a sample.  I purchased the $300 ProLon FMD for myself online.  (Still can't believe I shelled out big bucks to starve myself.)  I hoped for benefit.  I have some pain from a bit of osteoarthritis in two fingers and my neck, and lowering inflammation might help me.  Losing weight wasn't my primary objective, but I figured it would be a nice side effect.  I'm turning 55 this week,  and my vanity continues.   Jeff and I already follow the Endothelial Health Program.  We eat whole, organic foods, mostly plants and no processed food, no dairy or gluten, so I was already in the right dietary zone.  Just had to halve my daily caloric intake.  Gulp.

The things I liked about ProLon were that it is a plant based and gluten free diet, shipped in a box right to my front door.  It was very easy to follow.  Each day had a separate carton, which was clearly labled with nutritional information and instructions.  You can learn more about the specifics of this diet here:   https://prolonfmd.com   The reason it is a five day fast is because it takes that long for the body to reprogram and for cells to rejuvenate.  Dr. Longo recommends doing this fast every three to four months.  I think I could handle it a few times a year.

I believe it would be pretty easy to hack this program and do it on my own now.  I have all of the caloric and nutrient info.  But it's nice to have the supplements and energy drink and everything timed and packaged.  Makes it easier to follow,  and you're less likely to stray, when you think about how much you spent.   The food was surprisingly palatable.  I loved the kale crackers, and the instant soups were hearty and filling.  The breakfast bar was nutty and satisfying to chew.  Olives for snacks was fine with me.  And the herbal teas were nice.   I felt better knowing Dr. Longo is donating the proceeds to charity.  He's a good guy.   Anyone who studies jazz guitar and wants people healthier without drugs is OK in my book.   link

How did I feel after 5 days of eating under 800 calories?  It's odd, I wasn't really hungry, except for one day.  I was surprisingly energized, and not fatigued.   The hardest part of this program was giving up my usual three cups of caffeinated coffee a day.  Prolon allows only one caffeinated drink per day, and this left me with a nasty caffeine withdrawal headache after day 1. However,  I didn't feel sluggish without the coffee and I guess that must be from the cortisone coursing through my body.   I was really hungry on day 3, and wanted to quit, but curiosity kept me going.  That, and a bit of pride.

Jeff said he felt guilty eating in front of me.  But he got over that and ate just fine!  I also had to prepare a big dinner for some friends who happened to be in town on Day 2,  and that was pretty hard.   Standing over the stove, cooking and serving a delicious meal and then sitting and watching eveyone happily eating while I sipped herbal tea is not something I want to do again.

Now for the good stuff.  I slept really well, and am still having very vivid, lucid dreams.   I wake up ready to go, not groggy at all.   And my skin looks great!  It could be the fact I didn't had any alcohol, sugar or animal products for 5 days, but my eye bags are less noticeable and my complexion looks rosy.  And my arthritis pain is much, much better.  My knuckles are less stiff, and my neck has been feeling great.  I was able to keep active, out walking, running errands and doing my normal routine, without feeling faint. I didn't have any recording or performing work during this week, so I could take it relatively easy.  And I lost three pounds!  Not as much as many others report (average loss is 5 lbs.) but hey, I'll take it.

Final thoughts.  What we eat matters.  Our bodies are miraculous machines, and it makes sense that the manner in which we fuel ourselves has repercussions on our health.  By putting the body in a fasting state, we kick it into survival mode.  We were created to withstand periods with limited caloric intake, and our body knows how to utilize our stored sugars and fats reserves. Most of us in the industrialized western nations eat much more than we need, far too many processed foods,  too much animal protein and sugar,  and not enough plants.

But this isn't to cast blame for being sick!  No one gives themselves MS, cancer, osteoarthritis, or Alzheimer's.  We don't control our genetic predispositions, and we all will die eventually.   Here's Dr. Longo's TedX talk about how "if one disease doesn't get you, another one will!"   He shows that it is possible to live longer, healthier lives.  link   There are things in our control which we can do to feel better, function better, and maybe even heal,  including fasting. I believe the future will provide more understanding of our microbiome and brain, and how they are connected via the thousands of miles of lymph and blood vessels which keep our organs protected, nourished and cleansed.  And a lot of that depends on food.

Also, as it is the Lenten season, I couldn't help but feel more meaning to the fast.  Christians are taught to fast or give up something during Lent, to remind ourselves of Christ's forty days of fasting, praying and temptation in the desert before his eventual arrest and crucifixion.  This is practiced, not as an exercise in self-denial, but in order to draw closer and more reliant on God. And for that reminder, I am thankful.

Joan